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| Targets |
AM 103 targets 5-lipoxygenase-activating protein (FLAP), a membrane-associated protein that is essential for the activity of 5-lipoxygenase (5-LO) in the biosynthesis of leukotrienes. By inhibiting FLAP, AM 103 blocks the translocation of 5-LO to the nuclear membrane and prevents the production of pro-inflammatory leukotrienes including LTB₄ and cysteinyl leukotrienes (CysLTs).
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| ln Vitro |
AM 103's IC50 result in a human blood LTB4 inhibition test was 349 nM. When it comes to the five most prevalent CYP isoforms, AM 103 has good CYP characteristics; its IC50 values for CYP2D6 are greater than 30 μM, while those for CYP 3A4, 2C9, 2C19, and 1A2 are greater than 50 μM [1]. With IC50 values of 350, 113, and 117 nM for ionophore-stimulated LTB4 in human, rat, and mouse whole blood, respectively, AM103 is a new, powerful, and specific FLAP inhibitor [2].
In vitro, AM 103 is a potent FLAP inhibitor with an IC₅₀ value of 4.2 nM in biochemical assays. In human whole blood assays, it shows an IC₅₀ of 349 nM for LTB₄ inhibition. The compound selectively inhibits FLAP without directly affecting 5-LO activity. It has been used in biochemical and cellular assays to probe leukotriene biosynthesis and inflammation-related signaling pathways. The compound demonstrates high purity suitable for research applications. |
| ln Vivo |
In dogs, AM 103 exhibits a long intravenous half-life (5.2 h), low clearance (2.9 mL/min/kg), modest volume of distribution (0.41 L/kg), and excellent bioavailability (64%). AM 103 (10 mg/kg qd) lowers IL-5 levels to the levels attained after administering saline alone to mice, and it suppresses the rise in CysLT and EPO by around 60% [1]. With an estimated EC50 of about 60 nM, AM103 (1 mg/kg, po) demonstrated >50% inhibition for up to 6 hours in an ex vivo rat whole blood calcium ionophore-induced LTB4 test. AM 103 reduced the synthesis of cysteinyl leukotriene (CysLT) and LTB4 in rat lungs when they were exposed to calcium ionophores in vivo, with ED50 values of 0.8 and 1 mg/kg, respectively. With an EC50 of about 330 nM, AM103 from plasma inhibits LTB4 and CysLT in this model. AM103 decreased the levels of eosinophil peroxidase, CysLT, and interleukin-5 in bronchoalveolar lavage fluid in a model of chronic lung inflammation in BALB/c mice primed and challenged with ovalbumin. Lastly, animals given deadly intravenous doses of platelet-activating factor have longer life times when AM 103 is administered [2].
In vivo, AM 103 inhibits LTB₄ and cysteinyl leukotriene (CysLT) production with ED₅₀ values of 0.8 and 1 mg/kg, respectively, when rat lung is challenged with calcium ionophore. These findings demonstrate the compound's ability to block leukotriene synthesis in living organisms and support its potential for treating inflammatory conditions such as asthma and cardiovascular disease. The compound is being developed by Amira for therapeutic applications. |
| Enzyme Assay |
For non-cell enzyme/receptor binding assays, FLAP inhibition by AM 103 is assessed using membrane preparations or purified FLAP protein. The compound is incubated with FLAP and 5-LO in the presence of arachidonic acid and ATP. LTB₄ production is measured by ELISA or LC-MS/MS to determine the inhibitory activity. Radioligand binding assays using [³H]FLAP ligands can also be employed to assess direct binding affinity. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
For in vitro cell-based assays, AM 103 activity is assessed in human whole blood or isolated leukocyte cultures. Cells are stimulated with calcium ionophore or other agonists to induce leukotriene production. The compound is added at various concentrations, and LTB₄ and CysLT levels in the supernatant are measured by ELISA or LC-MS/MS. The inhibitory concentration (IC₅₀) is determined from dose-response curves. The compound can also be tested in cell lines expressing FLAP.
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| Animal Protocol |
For in vivo animal experiments, AM 103 is typically administered orally or intravenously to rats or other rodent models. Lung challenge models using calcium ionophore are employed to assess leukotriene inhibition. Following compound administration, animals are challenged with the ionophore, and bronchoalveolar lavage fluid or plasma is collected. LTB₄ and CysLT levels are measured to determine the ED₅₀ values for inhibition of leukotriene production in vivo.
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Orally absorbed well. AM 103 has a molecular weight of 631.76 g/mol and molecular formula C₃₆H₃₈N₃NaO₄S. The compound is provided in small milligram quantities (e.g., 5 mg) for research applications. It is soluble in DMSO and other organic solvents. Pharmacokinetic studies indicate the compound has suitable oral bioavailability for in vivo efficacy studies. Storage should be at -20°C for long-term stability. |
| Toxicity/Toxicokinetics |
AM 103 is an investigational compound not yet approved for clinical use. Toxicity data are limited to preclinical studies. As a FLAP inhibitor, it may affect leukotriene-dependent immune functions. Standard safety precautions for handling research chemicals should be followed. The compound is for research use only and not for human therapeutic application. The safety profile in humans has not been established pending clinical trials.
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| References |
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| Additional Infomation |
AM103 is a novel 5-lipoxygenase-activated protein (FLAP) inhibitor that treats asthma and cardiovascular disease by inhibiting the synthesis of leukotrienes (LT), substances that trigger inflammation. This drug was developed by Amira. Indications: For the treatment of asthma and cardiovascular disease. Mechanism of Action: Its exact mechanism of action is not fully understood, but AM103 inhibits 5-lipoxygenase-activated protein (FLAP). This prevents the synthesis of leukotrienes (LT), which typically trigger inflammation. Pharmacodynamics: Phase I clinical trial results showed that AM103 is safe and well-tolerated at daily doses up to 1000 mg, with no significant side effects observed. Pharmacodynamic data showed a dose-dependent significant reduction in LTB4 and LTE4 levels.
AM 103 is an investigational FLAP inhibitor being developed by Amira Pharmaceuticals for the treatment of asthma and cardiovascular disease. The compound has demonstrated potential in preclinical models by preventing leukotriene synthesis. It has not yet received regulatory approval for clinical use. The compound is available for research purposes only to study leukotriene biosynthesis and inflammation-related signaling pathways. No clinical trials have been completed for this compound. |
| Molecular Formula |
C36H38N3NAO4S
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| Molecular Weight |
631.759398937225
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| Exact Mass |
631.248
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| CAS # |
1147872-22-7
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| PubChem CID |
59248882
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.943
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
45
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| Complexity |
927
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
NJJMCCVPHCNMPB-UHFFFAOYSA-M
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| InChi Code |
InChI=1S/C36H39N3O4S.Na/c1-35(2,3)44-33-29-19-28(43-23-27-9-7-8-18-37-27)15-16-30(29)39(31(33)20-36(4,5)34(40)41)22-24-10-12-25(13-11-24)26-14-17-32(42-6)38-21-26;/h7-19,21H,20,22-23H2,1-6H3,(H,40,41);/q;+1/p-1
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| Chemical Name |
sodium;3-[3-tert-butylsulfanyl-1-[[4-(6-methoxypyridin-3-yl)phenyl]methyl]-5-(pyridin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~200 mg/mL (~316.58 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (7.91 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (7.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5829 mL | 7.9144 mL | 15.8288 mL | |
| 5 mM | 0.3166 mL | 1.5829 mL | 3.1658 mL | |
| 10 mM | 0.1583 mL | 0.7914 mL | 1.5829 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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